Understanding the evolutionary relationships and ongoing evolutionary dynamics of the medically extremely important Anopheles gambiae complex in Africa is of primary importance in any attempts to control malaria by controlling the vector populations of the disease. Recent advances in molecular evolutionary genetics now make it possible to approach such complex problems in greater detail and with more powerful tools than heretofore available. In particular we are interested in the Comparative evolution of the six presently recognized sibling species of the gambiae complex in relation to their chromosomal inversion polyorphisms. It is clear from other recent studies that inversion polymorphisms can complicate phylogenetic interpretations and, given the ubiquity of inversions in the gambiae complex, any phylogenetic analysis must consider the dynamics and history of the inversions. Thus, in addition to the medical relevance, the study has basic implications for understanding DNA sequence evolution in the presence of structural chromosomal polymorphism. More specifically, we propose to exploit the rapidly developing physical map of the Anopheles genome to study DNA markers within inversions and those outside inversions. Markers on the three independently segregating chromosomes will be studied. Thus we should be able to determine what the most probable species phylogeny is based on molecular divergence and compare it to DNA markers which reflect the history of the inversion polymorphisms. This will allow us to determine if the inversion polymorphisms are older than species, whether each species have independently evolved similar polymorphisms, etc. Of particular concern is the possibility of introgression between species, especially between the two most important species from an epidemiological perspective, gambiae sensu stricto and arabensis. The direction of introgression can he inferred by studies of mitochondrial DNA polymorphisms. Obviously, indications of introgression of genetic material across species boundaries have important implications for any attempts to genetically manipulate vector populations in order to control diseases.